A human infected with mycobacterium tuberculosis (Mtb) may be a hidden because an individual is asymptomatic. Someone with an active tuberculosis infection typically shows symptoms of a chronic cough and blood-tinged sputum referred to as a pulmonary active tuberculosis (ATB) infection. The asymptomatic or latent tuberculosis infections (LTBI) often do not progress to ATB for an individual with a healthy immune system. However, those with a compromised immune system, such as the elderly and those with HIV, have a much higher chance of developing life threatening ATB.
The standard treatment regimen for drug-susceptible TB consists of a 2-month intensive phase with isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE), followed by a 4-month continuation phase with isoniazid and rifampicin (HR). Conversion to a negative sputum culture after treatment initiation is currently the most objective indicator of response to treatment; however, this method takes 3 to 6 weeks for results. Additionally, sputum smears are not highly accurate with a high proportion of tuberculosis (TB) cases resulting in false negatives. Nucleic acid amplification-based tests are more sensitive, but do not differentiate between live and dead Mtb limiting the effectiveness in monitoring treatment-mediated clearance of Mtb. Existing blood-based tests, such as IFN-γ release assays (IGRAs), measure IFN-γ+ production in response to stimulation with Mtb-specific antigens ESAT6 and CFP10 and are specific for Mtb infection. However, IGRAs (e.g., QuantiFERON or T-SPOT.TB) do not discriminate between ATB and latent Mtb infection (LTBI) and are inadequate for monitoring treatment response. Thus, there is a need for identifying improved ways of monitoring the effectiveness of TB treatment.
Vigano et al. report expression of CD38 on CD8 T cells predicts maintenance of high viraemia in HAART-treated HIV-1-infected children. Highly active antiretroviral therapy, Lancet, 1998, 352(9144):1905-1906.
Janssens et al. report quantitative scoring of an interferon-γ assay for differentiating active from latent tuberculosis. Eur Respir J, 2007, 30(4):722-728.
Wallis et al. report biomarkers for tuberculosis disease activity, cure, and relapse. Lancet Infect Dis, 2009, 9(3):162-172.
Berry et al. report an interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 2010, 466(7309):973-977.
Bloom et al. report transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers. PLoS One, 2013, 8(8):e70630.
Riou et al. report a subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion. PLoS One, 2014, 9(7):e102178.
References cited herein are not an admission of prior art.